Cu(OTf)₂ catalyzed three component strategy for the synthesis of thienopyridine containing spirooxindoles and their cytotoxic evaluation

Synthesis of novel spirooxindoles via a three component reaction of thienopyridines, isatins and malononitriles under copper catalysis was accomplished. This one-pot, room temperature protocol allowed the synthesis of diversely substituted spirooxindoles in good to excellent yields. Cytotoxicity towards COLO320 cells revealed that compound 5v possessing a 2,6-difluorobenzyl group (IC₅₀ of 49.1 μM) was found to be highly potent among the screened compounds. In addition, molecular docking of compound 5v into caspase-3 receptors exhibited the largest binding energy (-10.5 kcal mol^-1) compared to other compounds. The formation of a DNA ladder for compound 5v also supports the experimental results.